Hemoglobin S polymerization is determined by the oxygen saturation, hemoglobin concentration and hemoglobin composition. Within the erythrocyte, hemoglobin polymerization can lead to abnormal rheology. Evaluation of the polymerization potential of a whole cell population has been difficult due to heterogeneity in hemoglobin concentration and hemoglobin composition. These heterogeneities are reflected in the broad density distribution of sickle erythrocytes and the variable distribution of fetal hemoglobin. We are now working on an analysis of sickle hemoglobin polymerization that would enable us to explicitly consider cell heterogeneity in hemoglobin concentration, composition, and possibly even oxygen affinity. Such an analysis would be useful not only in evaluation of individual sickle cell patients, but also in assessment of therapeutic strategies which alter hemoglobin concentration or hemoglobin composition, and in the evaluation of the transgenic mouse model for sickle cell disease with mixtures of sickle hemoglobin and mouse hemoglobins.